Matrix Metalloproteinase 2 (MMP2) and MMP9 Are Produced by Kidney Collecting Duct Principal Cells but Are Differentially Regulated by SV40 Large-T, Arginine Vasopressin, and Epidermal Growth Factor

Piedagnel, Rémi; Murphy, Gillian; Ronco, Pierre; Lelongt, Brigitte

doi:10.1074/jbc.274.3.1614

Cited by 46 publications

(49 citation statements)

References 66 publications

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“…These findings must be interpreted in light of the generally low levels of MMP-9 mRNA expression and activity. The absence of MMP-9 activity in the presence of detectable mRNA levels may be explained by posttranscriptional regulation of MMP-9 (Piedagnel et al 1999). TIMP-1 expression roughly paralleled the expression of MMPs, in agreement with reports on thyroid cancer cells and other cell types (Gomez et al 1997, Soula-Rothhut et al 2005.…”

Section: Discussionsupporting

confidence: 78%

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

Yeh¹,

Rougier²,

Park³

et al. 2006

Endocr Relat Cancer

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Mechanisms of invasion in thyroid cancer remain poorly understood. We hypothesized that signaling via the epidermal growth factor receptor (EGFR) stimulates thyroid cancer cell invasion by altering the expression and cleavage of matrix metalloproteinases (MMPs). Papillary and follicular carcinoma cell lines were treated with EGF, the EGFR tyrosine kinase inhibitor AG1478, and the MMP inhibitors GM-6001 and Col-3. Flow cytometry was used to detect EGFR. In vitro invasion assays, gelatin zymography, and quantitative reverse transcription-PCR were used to assess the changes in invasive behavior and MMP expression and activation. All cell lines were found to overexpress functional EGFR. EGF stimulated invasion by thyroid cancer cells up to sevenfold (P!0.0001), a process that was antagonized completely by AG1478 and Col-3, partially by GM-6001, but not by the serine protease inhibitor aprotinin. EGF upregulated expression of MMP-9 (2.64-to 8.89-fold, P!0.0001) and membrane type-1 MMP (MT1-MMP, 1.97-to 2.67-fold, P!0.0001). This effect was blocked completely by AG1478 and partially by Col-3. The activation of MMP-2 paralleled MT1-MMP expression. We demonstrate that MMPs are critical effectors of invasion in the papillary and follicular thyroid cancer cell lines studied. Invasion is regulated by signaling through EGFR, an effect mediated by augmentation of gelatinase expression and activation. MMP inhibitors and growth factor antagonists may be effective tumoristatic agents for the treatment of aggressive thyroid carcinomas.

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Section: Discussionsupporting

confidence: 78%

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

Yeh¹,

Rougier²,

Park³

et al. 2006

Endocr Relat Cancer

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“…MMP-3 is not detected in the proximal tubules of rats (71) but is expressed in the proximal and distal tubules of the monkey (60), as well as in the glomerulus and some tubular epithelial cells in humans (79). The expression of MMP-9 appears to be mainly confined to the glomerulus (39,46,55,71), although there are reports of expression in the proximal and distal tubules of the monkey (60) and in the rabbit collecting duct (62). MMP-13 and -14 are localized in the glomerulus in rats (84); however, these studies investigated mRNA expression in isolated glomeruli and did not investigate expression along the entire nephron.…”

Section: Renal Mmpsmentioning

confidence: 99%

Role of matrix metalloproteinases in renal pathophysiologies

Catania¹,

Chen²,

Parrish³

2007

American Journal of Physiology-Renal Physiology

348

314

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Matrix metalloproteinases (MMPs) are a large family of proteinases that remodel extracellular matrix (ECM) components and cleave a number of cell surface proteins. MMP activity is regulated via a number of mechanisms, including inhibition by tissue inhibitors of metalloproteinases (TIMPs). Originally thought to cleave only ECM proteins, MMP substrates are now known to include signaling molecules (growth factor receptors) and cell adhesion molecules. Recent data suggest a role for MMPs in a number of renal pathophysiologies, both acute and chronic. This review will focus on the expression and localization of MMPs and TIMPs in the kidney, as well as summarizing the current information linking these proteins to acute kidney injury, glomerulosclerosis/tubulointerstitial fibrosis, chronic allograft nephropathy, diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma.acute kidney injury; chronic allograft nephropathy; diabetic nephropathy; glomerulosclerosis; MMP; polycystic kidney disease; tissue inhibitor of metalloproteinase; tubulointerstitial fibrosis; renal cell carcinoma MATRIX METALLOPROTEINASES (MMPs) are zinc-containing endopeptidases that are involved in remodeling the extracellular matrix (ECM) and are crucial for tissue development and homeostasis. All MMPs are multidomain enzymes, generally consisting of a prodomain, a catalytic domain, a hinge region, and a hemopexin-like domain. Most MMPs are secreted as proMMPs; activation usually requires cleavage of the prodomain by plasmin or other MMPs (88). The propeptide sequence contains a conserved cysteine switch (PRCGXPD) to stabilize and inhibit the catalytic zinc ion, which is bound in a conserved HEXGHXXGXXH motif (53). The hemopexin-like domain is characterized by a "propeller" of four twisted ␤-sheets, which are thought to confer substrate recognition (53). Together, the hinge region and the hemopexin-like domain unravel substrate proteins for subsequent degradation. Originally thought to cleave only ECM proteins, this family of enzymes is now known to cleave a number of non-ECM substrates as well. For example, cell adhesion molecules (cadherins and integrins) and both growth factors and their receptors (TGF-␤, FGF-R1) are targeted by MMPs (74).Tissue inhibitors of metalloproteinases (TIMPs) are endogenous, specific inhibitors that bind and inhibit MMPs. Four TIMPs (TIMP-1-4) have been identified in vertebrates; these proteins share a similar structure which fits into the active site of the MMP catalytic domain. TIMPs inhibit all MMPs, except TIMP-1, which does not inhibit . A number of other MMP inhibitors have been identified, including RECK (81), ␣2-macroglobulin (4), and tissue factor pathway inhibitor-2 (33).MMPs are classified into six groups based on substrate and sequence homology: collagenases, gelatinases, stromelysins, matrilysins, membrane-type matrix metalloproteinases and "other MMPs" (Fig. 1). Collagenases [MMP-1, -8 (neutrophil collagenase), -13, and -18 (Xenopus laevis collagenase)] cleave collagens I, II, and III at a...

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“…It is important to note that, in all of the animals injected with either Lp(a)/apo(a) or F1, the urinary fragments, if present, were comparable in size and smaller than those in the plasma, suggesting that in our mouse strain neither NE nor MMP-12 was involved in the second step degradation by the kidney perhaps by additional MMPs. In this regard MMP-2 and 9 have been reported in the renal tissue (27,28).…”

Section: Studies On the In Vitro Proteolytic Cleavage Of Lp(a)/apo(a)mentioning

confidence: 99%

Macrophage Metalloelastase, MMP-12, Cleaves Human Apolipoprotein(a) in the Linker Region between Kringles IV-4 and IV-5

Edelstein¹,

Shapiro

Klezovitch³

et al. 1999

Journal of Biological Chemistry

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In this study we found that macrophage metalloelastase, MMP-12 cleaves, in vitro, apolipoprotein(a) (apo ( ) who by combining chemical and immunochemical techniques provided evidence that urinary apo(a) was represented by fragments derived from its N-terminal region. When, following purification, these urinary fragments were injected intravenously into mice, they were excreted in the urine without an apparent change in size. The same authors also reported the presence in the plasma of apo(a) fragments unattached to apoB100. Upon their intravenous injection into mice, these fragments were rapidly excreted in the urine as smaller sized components (3). Taken together, the results were interpreted to indicate that the apo(a) fragments in human plasma are derived from Lp(a)/apo(a) and are in turn the source of the apo(a) fragments in the urine. Unanswered in those studies was the underlying cause of the apo(a) fragmentation as well as the site or sites for its occurrence. We reported previously that limited in vitro proteolysis of apo(a), by either pancreatic or leukocyte elastase, is attended by the cleavage at the Ile 3520 -Leu 3521 bond located in the linker domain between kringles IV-4 and IV-5 (4, 5). This cleavage generates two main fragments, one representing the N-terminal domain, F1, and the other the C-terminal domain, F2. When these two fragments were separately injected intravenously into mice, F1 but not F2 was rapidly excreted in the urine (4). This observation prompted us to examine whether the cleavage site on apo(a) was limited to serine proteases such as pancreatic and leukocyte or neutrophil elastase (NE) or could also apply to other inflammatory enzymes. Among them we considered matrix matalloproteinases (MMPs), which are metallo-dependent enzymes involved in the homeostasis of the extracellular matrix and also shown to play an important role in the atherosclerotic process (6 -13). In this work, we directed our attention to macrophage metalloelastase, also referred to as MMP-12, which was first identified as an elastolytic metalloproteinase secreted by inflammatory macrophages (14) and structurally defined (15,16). This enzyme has a broad substrate specificity for matrix macromolecules such as fibronectin, laminin, vitronectin, and proteoglycans (17). In the current study, we now show that MMP-12 cleaves apo(a) in vitro and also provide evidence that, in the mouse strain used, it is involved in the generation of F1 in vivo. EXPERIMENTAL PROCEDURESReagents-Human leukocyte elastase (EC 3.4.21.37) was purchased from Sigma. Antiserum to purified preparations of apo(a), Lp(a), and LDL were raised in the rabbit and affinity purified as described previously (18). Anti-Lp(a) were shown to be devoid of immunoreactivity to LDL and plasminogen; anti-LDL was unreactive to apo(a).Studies in Mice-Mice deficient in NE (NE Ϫ/Ϫ ) or MMP-12 (MMP-12 Ϫ/Ϫ ) in a pure 129/Svj background were generated by targeted disruption of either the NE or MMP-12 gene in RW4 embryonic stem cells as described previously (19,20). Al...

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Matrix Metalloproteinase 2 (MMP2) and MMP9 Are Produced by Kidney Collecting Duct Principal Cells but Are Differentially Regulated by SV40 Large-T, Arginine Vasopressin, and Epidermal Growth Factor

Cited by 46 publications

References 66 publications

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A

Role of matrix metalloproteinases in renal pathophysiologies

Macrophage Metalloelastase, MMP-12, Cleaves Human Apolipoprotein(a) in the Linker Region between Kringles IV-4 and IV-5

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